UrvKd S'.aies Ofnce o! ^es'.coes
Envron~-.er.ta! °roiection and Toxic Su'jstiT-.ce^
Agency (H7501G 540/FS-92-170
EPA Pesticide
Fact Sheet
Name of Chemical: CLETHODIM
Reason for Issuance: NEW CHEMICAL
Date ISSUed: January 28, 1992
Fact Sheet Number: 230
Description of Chemical
Chemical Name: (E)-(+)-2-[l-[[(3-Chloro-2-
Propenyl)oxy]imino]propyl]-5-[2-
(ethylthio)propyl]-3-hydroxy-2-cyclohexen-l-one
Common and Other Names: Clethodim
Trade Name: Select
EPA Shaughnessy Codes: 121011
Chemical Abstracts Service (CAS) No.: 99129-21-2
Year of Initial Registration: -1991
Pesticide Type: Herbicide
Chemical Family: Cyclohexanedione
U.S. and Foreign Producers: Valent U.S.A. Corporation
Use Patterns and Formulations
Application Sites-: Postemergent treatment on soybeans and cotton
for control of grasses
Types and Methods of Application: Foliar application by ground
equipment
Application Rates: 0.094 - 0.25 Ib ai/acre
Types of Formulations: 25% emulsifiable concentrate (EC)
Usual Carriers: Mix with water
Science Findings
Summary Science Statement
Review of the product chemistry, environmental fate,
toxicology, ecological effects and residue chemistry data have been
completed. The available data support conditional registration of
Select for control of annual and perennial grasses in soybeans and
cotton. Results of acute toxicity studies indicate Toxicity
Category III ^(Caution). Chronic studies present no evidence of
unacceptable 'health hazards resulting from the proposed uses
Ecological effects data indicate that the proposed use on cotton
and soybeans will result in minimal risk to avian, aquatic and
mammalian species.
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Clethodim and degradates do not show persistence in field
dissipation studies. No significant bioaccumulation occurs in fish.
Since it is easily degraded both by photolysis and aerobic
microbial action, clethodim does not seem likely to threaten
surface water. Under present use patterns and under most
circumstances, clethodim does not appear likely to threaten
groundwater.
Chemical Characteristics:
Technical
Physical State:
Molecular Weight:
Molecular Formula:
Color:
Viscous liquid
359.92
H
26
CINO-
Clear amber
Melting Point
Boiling Point
Density
*Solubility
Vapor pressure:
Dissociation
Octanol/water
partition coefficient:
PH
Flammability:
Explodability:
Storage Stability
Viscosity:
Miscibility
N/A
N/A
1.395 g/cu.cm 20 C
Limit, g/100 mL solvent at 25 C
1 x 10~7 torr
pK2 =4.47
Kow = 1.5 x 104
4.1 in a stirred solution
or 4.2 in a standing
solution 4.9 (5% aqueous
solution.
Flashpoint 110 *C
N/A
< 1% and < 3% degradation in glass
containers and aluminum containers,
respectively, after one year of
storage at 21 *C
100 cps at 20 'C
N/A
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Characteristics:
Dielectric Breakdown
Voltage:
Corrosiveness
N/A
N/A
N/A
Toxicology Characteristics:
t
Acute toxicology results:
(Technical (T) 83.3% & 96.ai:)
Acute oral toxicity-(rats): 98.6%
Acute oral toxicology-(rat): 83.3%
Acute oral LDso(mice) : 83.3%
Acute Dermal LD50(rabbit) 83.3%
Acute inhalation LD50 (rat): 83.3%
Primary eye irritation(rabbit) 83.3%
Primary dermal irritation(rabbit)
Acute Toxicity (Select Herbicide)
Acute oral toxicology-(rat): 26.1%
Acute oral LD50(rat): 26.1%
*
Acute Dermal LD50(rabbit) 26.0%
LD50(female) greater than
1.4 gm/kg category III
LD50(F)=1.36 gm/kg
toxicity category III
LD50(M) 1.63%g/kg
LD50(M)=2.57 g/kg
LD50(F) =2 . 43g/kg
toxicity category TTI
LD50(KaFji greater than
5 g/kg toxicity category
IV
LC50 greater than
3.9/L(M&F)tox.category
111
toxicity category III
toxicity category IV
26.1 and 26.0% ai)
LD50(F) 2.92g/kg
LD50(M) 3.61%g/kg
tox. category III
LD50(M)=3.61 g/kg
toxicity III
LD50(F)2.92g/kg
LD50(M&F) greater than
5 g/kg tox.category
IV
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Acute inhalation LC50(rat) : 26.1%*
Primary eye irritation
(rabbit):26.1%
Primary Dermal irritation
(rabbit): 26.0%
Dermal sensitization:
Subchronic Testing
LC50 greater than
5.4 mg/L(M&F)(0.33 mg/L)
toxicity category II
tox.category III
Nonsensitizer
21-Day Dermal (rat)- The systemic NOEL is 50 mg/kg/day. The
LOEL for skin is 10 mg/kg/day (26.3%).
Chronic Testing
Carcinogenicity
In the 18-month carcinogenicity study, mice administered
clethcdin (83.3%) at dosages of 0, 20, 200, 1000, or 3000 ppm
resulted in a systemfc NOEL and LOEL of 200 and 1000 ppm (HOT) for
male and female mice, respectively.
Chronic toxicity
In a 1-year feeding study, dogs were treated with clethodim
(83.3%) at dose levels of 0, 1, 75, or 300 mg/kg/day. The
systemic LOEL for both sexes is 75 mg/kg/day based on increased
absolute and relative liver weights and alterations in hematology
and clinical chemistry. The NOEL is 1 mg/kg/day.
Chronic toxicity/Carcinogenicitv - (Rats)
A 2-year chronic toxicity/carcinogenicity study with rats fed
clethodim (83%) at dosages of 0, 5, 20, 500, and 2500 ppm.
Liver weights were not affected at study termination nor were there
any compound-related histological changes noted (HOT). The
systemic NOEL is 500 ppm (19 mg/kg/day), based upon the liver
weights were not effected at the study termination nor were there
any compound-related histological changes noted. The systemic LOEL
is 2500 ppm (100 mg/kg/day).
•
Teratogenicitv
A rat teratology study was conducted with clethodim (82.6%)
using doses of 0, 10, 100, 350, and 700 mg/kg/day. Based upon
reductions in body weight gain and clinical signs of toxicity,
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the NOEL and LOEL for maternal toxicity are 100 and 350 mg/kg/day
respectively. Based on reductions in fetal body weight and
increases in skeletal anomalies the NOEL and LOEL for developmental
toxicity are 100 and 350 mg/kg/day, respectively.
A rabbit teratology study was conducted using doses of 0, 25,
100, and 300 mg/kg/day (clethodim 82.6%). Maternal toxicity was
manifested by clinical signs of toxicity, reduced weight gain and
food consumption during treatment. The NOEL and LOEL are 25 and
100 mg/kg/day, respectively. Developmental toxicity was not
observed. The NOEL for this endpoint is 300 mg/kg/day.
A rat teratology study was conducted using doses of 0, 10,
.100, and 700 mg/kg/day (clethodim 98.6%). The maternal NOEL and
LOEL are 10 and 100 mg/kg/day, respectively. Based upon
significant reductions in fetal body weight and litter size
significantly increased litter and fetal incidence of cervical rib
at 700 mg/kg/day, the NOEL and LOEL for developmental toxicity are
100 and 700 mg/kg/day, respectively.
Reproduction
In a reproductive toxicity study, rats were fed doses of 0, 5,
20, 500, or 2500 ppm. The NOEL and LOEL for systemic
toxicity are 500 ppm (51 mg/kg/day) and 2buu ppa I>DJ ag/kg/aay) >
respectively, based on reductions in body weight, particularly in
males, and decreased food consumption in both generations. No
effects on fertility, length of gestation, or growth and
development of offspring were observed. The NOEL for reproductive
toxicity is 2500 ppm (HOT) (83.3%).
Mutaqenicity
Technical material was not mutagenic in the Ames assay.
Metabolism - Rats
The requirement for a metabolism study in rats has been
satisfied. Five groups of rats, 5 males and 5 females, were
dosed in various sequences with either 4.5 or 450 mg/kg [14C]
clethodim orally.
Clethodim is readily absorbed and eliminated with essentially
all of the [ C] dose recovered from urine. Several days after the
compound was« administered, smaller amounts were recovered from
feces (9-17%) and expired air. Gastrointestinal absorption was
estimated at 89-96%. There was no evidence of bioconcentration
following multiple exposures; the adrenal dosing had the highest
concentration of radiolabel (0.07 to 0.22 ppm for low and repeated
doses; 5.4 to 13 ppm for high-dose rats). Clethodim was extensively
metabolized with < 1 percent eliminated
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as the unchanged parent compound. The predominant metabolite
recovered was clethodim sulfoxide (48 to 63% of administered label
after 48 hours).
Environmental Characteristics
Hydrolysis: Propyl [ C]-clethodim degraded with half-lives of
26 days (pH 5) and approximately 300 days (pH 7 and 9).
Allyl-labeled clethodim degraded with half-lives of 42 days(pH 5)
and 360 days (pH 7). The degrades were clethodim.oxazole. and
l-chloropropen-3-ol.
Aerobic Soil Metabolism- Under aerobic soil conditions,
clethodim degrades with a half-life of 1 to 2.6 days.
Anaerobic Acruatic Metabolism - Results of the anaerobic
aquatic metabolism study indicate that clethodim has a half-life of
128 days in the aqueous phase and 214 days in the sediment. The
degradates formed are metabolized as rapidly as they are formed,
and do not appear to accumulate.
*
Aqueous Photolysis - Clethodim degrades with half-lives of
1.5-9.3 days, at pH 5 and 9, respectively.
Mobility - Leaching and absorption/desorption. Clethodim and
its sulfoxide, sulfone, and oxazole sulfone degradates are weakly
absorbed into two sandy loam soils, clay loam, sandy clay loam, and
sandy soil. . .
Soil Photolysis - Photolysis of clethodim on soil will not be
a major pathway of degradation, since metabolism is rapid. After
7 days, less than 6.8% of parent compound remained. Little or no
volatile material, organic or C02 was produced. The single major
product was clethodim sulfoxide. Metabolism is the primary
mechanism of degradation.
Terrestrial Field Dissipation - No vertical movement of the
residues was observed as all measurable residues were confined to
the top 20 cm of the soil.
Accumulation - In Confined Rotational Crop and in Fish - In
rotational crops, some uptake and concentration were detected at an
exaggerated rate of 4 X the maximum single application. Closely -
related metabolites accounted for around 1/3 of the total
radioactivity observed in the plants. No significant
bioaccumulation occurred in fish.
Ecological Characteristics:
Available fish and wildlife data indicate that the proposed
uses on cotton and soybeans will result in minimal hazard to
nontarget and endangered beneficial insect, avian, freshwater
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fish and mammalian species.
Clethodim is slightly to practically non-toxic to birds . The
avian acute oral LD50 was greater than 2000 mg/kg for the bobwhite
quail and the avian dietary LC50is were > 4270 ppm for the bobwhite
quail and > 3978 ppm for the mallard duck. The mallard and avian
reproduction study is acceptable and fulfills the waterfowl
guideline requirement. An NOEL of 1000 ppm was reported.
Clethodim technical is slightly toxic to cold-and warm-water
fish species. The fish LC50 for the rainbow trout is 18.0 ppm and
33.0. ppm for the blueqill sunfish. Select EC is slightly toxic to
Daphnia macrna. The 48 hour UC$Q value for Daphnia magna is 20.2
mg/L; and the NOEL is 5.5 mg/L. The formulated product was tested
because of a high level of a certain inert ingredient in the
formulation.
Clethodim technical and Select 2 EC are practically non-toxic
to honeybees,with an LD50 of greater than 100 ug/bee. Select 2 EC
was evaluated to assess the toxicity of formulation inerts.
Tier I and II non-target plant phytotoxicity data using
technical Clethodim were submitted. The data demonstrate that
Select 2 EC is extremely selective in its mode of action. Only
grass species are at risk from off-target movement. Endangered
grass in or arenni Select-1-re?_*•?? *'<. ^H«JV f^om around or
aerial applications. Thus, Select is prohibited from use in the
counties listed under "Summary ox Regulatory Positions."
Tolerance Assessment - A tolerance with an expiration date is
established for residue of the herbicide Clethodim (ANSI) , (Ł)-(+)-
2-[l[[(3-chloro-2-propenyl)oxy]imino]-propyl]-5-[2-
(ethylthio)propyl]-3-hydroxy-2-cyclohexen-l-one, and its
metabolites containing the 2-
cyclohexen-1-one moiety in/on soybeans at 10 ppm; cottonseed at 1
ppm; meat, fat, and meat byproducts of cattle, goats, hogs, horses,
poultry, and sheep at 0.2 ppm; milk at 0.05 ppm; eggs at 0.2 ppm;
soybean soapstock at 15 ppm; and cottonseed meal at 2 ppm.
Summary of Regulatory Positions
Use, formulation, manufacturing process or geographical
restriction: " Do not apply directly to water," "Do not apply
where runoff is likely to occur.11 "Do not apply where weather
conditions favor drift from areas treated. Do not allow Select to
come in contact with desirable grass crops such as corn, rice,
sorghum, small grains, or turf as these other grass crops will be
injured or killed." "Minor leaf spotting may occur on soybeans and
cotton under certain environmental conditions. New foliage is not
affected." Do not apply a broadleaf (herbicide) within one day
following application. Do not apply by air."
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Select 2EC is prohibited from use in the following counties to
avoid non-target injury to the endangered grass species listed: (1)
Solano grass-Colusa, Contra, Costa, Fresno, Glenn, Madera, Merced,
San Joaquin, Solano, Stanislaus and Tehama Counties in California,
and (2) Texas wild rice - Hays county in Texas."
Summary of Maior Data Gaps
Revise analytical method and have a successful independent
laboratory validation conducted on the revised method.
Contact Person at EPA
Joanne I. Miller
Product Manager (23)
Fungicide-Herbicide Branch
Registration Division (H7505C)
Office of Pesticide Programs
Environmental Protection Agency
401 M Street SW.
Washington, DC 20460
Office location and telephone number:
Pan. 245, Crystal Mall #2
1921 Jefferson Davis Highway
Arlington, VA 22202
(703) 305-783.0 . . , :. .
Disclaimer: The information in this Pesticide Fact Sheet is
a summary only and is not to be used to satisfy data requirements
for pesticide registration and reregistration. The complete
Registration Standard for the pesticide may be obtained from the
contact person listed above.
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